Steroid resistant Minimal change disease : Focal segmental
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Transcript Steroid resistant Minimal change disease : Focal segmental
Nephrology Diseases &
Chemotherapy
Idiopathic Nephrotic
Syndrome (NS)
Caused by renal diseases that increase the
permeability across the glomerular filtration
barrier.
Characterized (first two are used diagnostically
because the last two may not be seen in all
patients) by:
1. Nephrotic range proteinuria - Urine
protein excretion >50 mg/kg per day
2. Hypoalbuminemia - Serum albumin <3
g/dL (30 g/L)
3. Edema
4. Hyperlipidemia
Idiopathic Nephrotic
Syndrome (NS)
Two Common Types:
1. Steroid Resistant Minimal Residual
Disease (MCD) with peak age
between 2-3 years
2. Focal Segmental Glomerulosclerosis
(FSGS) with peak age commonly seen
at a later age.
Pathophysiology
The exact pathogenesis remains unclear.
Possible theories postulated point to role of
lymphokines and T cells
Immunosupressive therapies are used because of
interlukine and T cell involvement.
1. Alkylating agents : Cyclophosphamide or
Chlorambusil
2. Combination immunosuppression:
Vincristine+cyclophosphamide+prednisone.
3. Cyclosporine
4. Cellcept or Prograf
Membranous Nephropathy
It is a antibody mediated disease with
unclear mechanism
Treatment strategies involve:
1. Chlorambucil + Prednisone
2. Cyclosporine + Prednisone
3. Cellcept+ Prednisone
4. Rituximab
Recent report indicate that patient treated
with CD 20 had remission and reversal of
pathological changes in the follow up biopsy.
Systemic Vasculitis with
Kidney Involvement
Types of Vasculitis:
1. Polyarteritis Nodosa: Necrotizing
inflammation of medium sized or small
arteries without glomerulonephritis or
vasculitis in arterioles, capillaries or
venules.
2. Kawasaki disease: Arteritis affecting
large, medium and small arteries.
Systemic Vasculitis with
Kidney Involvement
3. Wegners’s Granulomatosis:
Granulomatous inflammation involving
respiratory tract and necrotizing vasculitis
of the small to medium vessel.
Glomerulonephritis is common.
4. Microscopic polyangitis: Necrotizing
vasculitis affecting small vessel and causing
glomerulonephritis
Pathogenesis
Vasculitis is caused by the activation of
inflammatory mediator systems in vessel
walls.
Putative immunologic causes of vasculitis:
1. Immune complex Mediated
2. Antineutrophil cytoplasmic antibody
mediated
3. Cell mediated
Treatment
Treatment strategies are based on
counteracting the immunogenic stimulus:
1. High dose solumedrol
2. Cyclophosphamide
3. Azathioprine
4. Plasmapheresis
5. Newer agents like Cellcept are being
used for treatment of relapse, CD20
antibodies, severe disease and/or relapse
Kidney Transplant
T8 cells are predominant T cells involved in
kidney rejection.
Henceforth, protocols involve usage of:
1. Antithymocyte globulin
2. Monoclonal anti CD 25 antibodies
3. Prograf and
4. Cellcept.
Although all these agents have different mode of
action, they all mitigate the T cell proliferation
or depletion.
Kidney Transplant
Antibody mediated rejection is less
commonly encountered but, carries a
very high graft loss or dysfunction.
Treatment involves:
1. Plasmapheresis and
2. CD 20 antibodies (i.e.Rituximab)
Small Vessel: Immune complex vasculitis
Henoch Shonlein Purpura (HSP)
One if the most common Vasculitides in Children
Clinical Manifestations
◦ Palpable purpura: key to diagnosis; most common lower
extremities and buttocks, color variation from red, purple,
brown coloration
◦ Arthritis/arthralgia: 50-80%, usually large joints
◦ Glomerulonephritis: 1/3 of children have some level renal
involvement
Microscopic hematuria and mild proteinuria most common
10% have severe nephrotic syndrome
◦ GI involvement: 2/3 of children have some type of involvement
Abdominal pain
Gastrointestinal hemorrhage
Cassidy, 2005
Henoch Shonlein Purpura (HSP)
•
Criteria for diagnosis : at least two of the following
criteria
–
–
–
–
•
Palpable purpura
Less than 20 years old at onset
Bowel angina
Wall granulocytes on biopsy
Treatment
– Supportive: hydration, nutrition, and pain control
– Occasionally short term steroid burst
– In presence of severe disease: steroids, cytotoxic medication
•
Prognosis
– 2/3 resolve within 4 weeks
– 1/3 have re-occurrences between 6wks to 2 years on onset
Cassidy, 2005
Small Vessel: Immune complex vasculitis
Henoch Shonlein Purpura (HSP)